More on Science
Michael Hunter, MD
3 years ago
5 Drugs That May Increase Your Risk of Dementia
While our genes can't be changed easily, you can avoid some dementia risk factors. Today we discuss dementia and five drugs that may increase risk.
Memory loss appears to come with age, but we're not talking about forgetfulness. Sometimes losing your car keys isn't an indication of dementia. Dementia impairs the capacity to think, remember, or make judgments. Dementia hinders daily tasks.
Alzheimers is the most common dementia. Dementia is not normal aging, unlike forgetfulness. Aging increases the risk of Alzheimer's and other dementias. A family history of the illness increases your risk, according to the Mayo Clinic (USA).
Given that our genes are difficult to change (I won't get into epigenetics), what are some avoidable dementia risk factors? Certain drugs may cause cognitive deterioration.
Today we look at four drugs that may cause cognitive decline.
Dementia and benzodiazepines
Benzodiazepine sedatives increase brain GABA levels. Example benzodiazepines:
Diazepam (Valium) (Valium)
Alprazolam (Xanax) (Xanax)
Clonazepam (Klonopin) (Klonopin)
Addiction and overdose are benzodiazepine risks. Yes! These medications don't raise dementia risk.
USC study: Benzodiazepines don't increase dementia risk in older adults.
Benzodiazepines can produce short- and long-term amnesia. This memory loss hinders memory formation. Extreme cases can permanently impair learning and memory. Anterograde amnesia is uncommon.
2. Statins and dementia
Statins reduce cholesterol. They prevent a cholesterol-making chemical. Examples:
Atorvastatin (Lipitor) (Lipitor)
Fluvastatin (Lescol XL) (Lescol XL)
Lovastatin (Altoprev) (Altoprev)
Pitavastatin (Livalo, Zypitamag) (Livalo, Zypitamag)
Pravastatin (Pravachol) (Pravachol)
Rosuvastatin (Crestor, Ezallor) (Crestor, Ezallor)
Simvastatin (Zocor) (Zocor)
This finding is contentious. Harvard's Brigham and Womens Hospital's Dr. Joann Manson says:
“I think that the relationship between statins and cognitive function remains controversial. There’s still not a clear conclusion whether they help to prevent dementia or Alzheimer’s disease, have neutral effects, or increase risk.”
This one's off the dementia list.
3. Dementia and anticholinergic drugs
Anticholinergic drugs treat many conditions, including urine incontinence. Drugs inhibit acetylcholine (a brain chemical that helps send messages between cells). Acetylcholine blockers cause drowsiness, disorientation, and memory loss.
First-generation antihistamines, tricyclic antidepressants, and overactive bladder antimuscarinics are common anticholinergics among the elderly.
Anticholinergic drugs may cause dementia. One study found that taking anticholinergics for three years or more increased the risk of dementia by 1.54 times compared to three months or less. After stopping the medicine, the danger may continue.
4. Drugs for Parkinson's disease and dementia
Cleveland Clinic (USA) on Parkinson's:
Parkinson's disease causes age-related brain degeneration. It causes delayed movements, tremors, and balance issues. Some are inherited, but most are unknown. There are various treatment options, but no cure.
Parkinson's medications can cause memory loss, confusion, delusions, and obsessive behaviors. The drug's effects on dopamine cause these issues.
A 2019 JAMA Internal Medicine study found powerful anticholinergic medications enhance dementia risk.
Those who took anticholinergics had a 1.5 times higher chance of dementia. Individuals taking antidepressants, antipsychotic drugs, anti-Parkinson’s drugs, overactive bladder drugs, and anti-epileptic drugs had the greatest risk of dementia.
Anticholinergic medicines can lessen Parkinson's-related tremors, but they slow cognitive ability. Anticholinergics can cause disorientation and hallucinations in those over 70.
5. Antiepileptic drugs and dementia
The risk of dementia from anti-seizure drugs varies with drugs. Levetiracetam (Keppra) improves Alzheimer's cognition.
One study linked different anti-seizure medications to dementia. Anti-epileptic medicines increased the risk of Alzheimer's disease by 1.15 times in the Finnish sample and 1.3 times in the German population. Depakote, Topamax are drugs.
Bob Service
3 years ago
Did volcanic 'glasses' play a role in igniting early life?
Quenched lava may have aided in the formation of long RNA strands required by primitive life.
It took a long time for life to emerge. Microbes were present 3.7 billion years ago, just a few hundred million years after the 4.5-billion-year-old Earth had cooled enough to sustain biochemistry, according to fossils, and many scientists believe RNA was the genetic material for these first species. RNA, while not as complicated as DNA, would be difficult to forge into the lengthy strands required to transmit genetic information, raising the question of how it may have originated spontaneously.
Researchers may now have a solution. They demonstrate how basaltic glasses assist individual RNA letters, also known as nucleoside triphosphates, join into strands up to 200 letters long in lab studies. The glasses are formed when lava is quenched in air or water, or when melted rock generated by asteroid strikes cools rapidly, and they would have been plentiful in the early Earth's fire and brimstone.
The outcome has caused a schism among top origin-of-life scholars. "This appears to be a great story that finally explains how nucleoside triphosphates react with each other to create RNA strands," says Thomas Carell, a scientist at Munich's Ludwig Maximilians University. However, Harvard University's Jack Szostak, an RNA expert, says he won't believe the results until the study team thoroughly describes the RNA strands.
Researchers interested in the origins of life like the idea of a primordial "RNA universe" since the molecule can perform two different functions that are essential for life. It's made up of four chemical letters, just like DNA, and can carry genetic information. RNA, like proteins, can catalyze chemical reactions that are necessary for life.
However, RNA can cause headaches. No one has yet discovered a set of plausible primordial conditions that would cause hundreds of RNA letters—each of which is a complicated molecule—to join together into strands long enough to support the intricate chemistry required to kick-start evolution.
Basaltic glasses may have played a role, according to Stephen Mojzsis, a geologist at the University of Colorado, Boulder. They're high in metals like magnesium and iron, which help to trigger a variety of chemical reactions. "Basaltic glass was omnipresent on Earth at the time," he adds.
He provided the Foundation for Applied Molecular Evolution samples of five different basalt glasses. Each sample was ground into a fine powder, sanitized, and combined with a solution of nucleoside triphosphates by molecular biologist Elisa Biondi and her colleagues. The RNA letters were unable to link up without the presence of glass powder. However, when the molecules were mixed with the glass particles, they formed long strands of hundreds of letters, according to the researchers, who published their findings in Astrobiology this week. There was no need for heat or light. Biondi explains, "All we had to do was wait." After only a day, little RNA strands produced, yet the strands continued to grow for months. Jan Paek, a molecular biologist at Firebird Biomolecular Sciences, says, "The beauty of this approach is its simplicity." "Mix the components together, wait a few days, and look for RNA."
Nonetheless, the findings pose a slew of problems. One of the questions is how nucleoside triphosphates came to be in the first place. Recent study by Biondi's colleague Steven Benner suggests that the same basaltic glasses may have aided in the creation and stabilization of individual RNA letters.
The form of the lengthy RNA strands, according to Szostak, is a significant challenge. Enzymes in modern cells ensure that most RNAs form long linear chains. RNA letters, on the other hand, can bind in complicated branching sequences. Szostak wants the researchers to reveal what kind of RNA was produced by the basaltic glasses. "It irritates me that the authors made an intriguing initial finding but then chose to follow the hype rather than the research," Szostak says.
Biondi acknowledges that her team's experiment almost probably results in some RNA branching. She does acknowledge, however, that some branched RNAs are seen in species today, and that analogous structures may have existed before the origin of life. Other studies carried out by the study also confirmed the presence of lengthy strands with connections, indicating that they are most likely linear. "It's a healthy argument," says Dieter Braun, a Ludwig Maximilian University origin-of-life chemist. "It will set off the next series of tests."
Will Lockett
3 years ago
The Unlocking Of The Ultimate Clean Energy
The company seeking 24/7 ultra-powerful solar electricity.
We're rushing to adopt low-carbon energy to prevent a self-made doomsday. We're using solar, wind, and wave energy. These low-carbon sources aren't perfect. They consume large areas of land, causing habitat loss. They don't produce power reliably, necessitating large grid-level batteries, an environmental nightmare. We can and must do better than fossil fuels. Longi, one of the world's top solar panel producers, is creating a low-carbon energy source. Solar-powered spacecraft. But how does it work? Why is it so environmentally harmonious? And how can Longi unlock it?
Space-based solar makes sense. Satellites above Medium Earth Orbit (MEO) enjoy 24/7 daylight. Outer space has no atmosphere or ozone layer to block the Sun's high-energy UV radiation. Solar panels can create more energy in space than on Earth due to these two factors. Solar panels in orbit can create 40 times more power than those on Earth, according to estimates.
How can we utilize this immense power? Launch a geostationary satellite with solar panels, then beam power to Earth. Such a technology could be our most eco-friendly energy source. (Better than fusion power!) How?
Solar panels create more energy in space, as I've said. Solar panel manufacture and grid batteries emit the most carbon. This indicates that a space-solar farm's carbon footprint (which doesn't need a battery because it's a constant power source) might be over 40 times smaller than a terrestrial one. Combine that with carbon-neutral launch vehicles like Starship, and you have a low-carbon power source. Solar power has one of the lowest emissions per kWh at 6g/kWh, so space-based solar could approach net-zero emissions.
Space solar is versatile because it doesn't require enormous infrastructure. A space-solar farm could power New York and Dallas with the same efficiency, without cables. The satellite will transmit power to a nearby terminal. This allows an energy system to evolve and adapt as the society it powers changes. Building and maintaining infrastructure can be carbon-intensive, thus less infrastructure means less emissions.
Space-based solar doesn't destroy habitats, either. Solar and wind power can be engineered to reduce habitat loss, but they still harm ecosystems, which must be restored. Space solar requires almost no land, therefore it's easier on Mother Nature.
Space solar power could be the ultimate energy source. So why haven’t we done it yet?
Well, for two reasons: the cost of launch and the efficiency of wireless energy transmission.
Advances in rocket construction and reusable rocket technology have lowered orbital launch costs. In the early 2000s, the Space Shuttle cost $60,000 per kg launched into LEO, but a SpaceX Falcon 9 costs only $3,205. 95% drop! Even at these low prices, launching a space-based solar farm is commercially questionable.
Energy transmission efficiency is half of its commercial viability. Space-based solar farms must be in geostationary orbit to get 24/7 daylight, 22,300 miles above Earth's surface. It's a long way to wirelessly transmit energy. Most laser and microwave systems are below 20% efficient.
Space-based solar power is uneconomical due to low efficiency and high deployment costs.
Longi wants to create this ultimate power. But how?
They'll send solar panels into space to develop space-based solar power that can be beamed to Earth. This mission will help them design solar panels tough enough for space while remaining efficient.
Longi is a Chinese company, and China's space program and universities are developing space-based solar power and seeking commercial partners. Xidian University has built a 98%-efficient microwave-based wireless energy transmission system for space-based solar power. The Long March 5B is China's super-cheap (but not carbon-offset) launch vehicle.
Longi fills the gap. They have the commercial know-how and ability to build solar satellites and terrestrial terminals at scale. Universities and the Chinese government have transmission technology and low-cost launch vehicles to launch this technology.
It may take a decade to develop and refine this energy solution. This could spark a clean energy revolution. Once operational, Longi and the Chinese government could offer the world a flexible, environmentally friendly, rapidly deployable energy source.
Should the world adopt this technology and let China control its energy? I'm not very political, so you decide. This seems to be the beginning of tapping into this planet-saving energy source. Forget fusion reactors. Carbon-neutral energy is coming soon.
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Ray Dalio
3 years ago
The latest “bubble indicator” readings.
As you know, I like to turn my intuition into decision rules (principles) that can be back-tested and automated to create a portfolio of alpha bets. I use one for bubbles. Having seen many bubbles in my 50+ years of investing, I described what makes a bubble and how to identify them in markets—not just stocks.
A bubble market has a high degree of the following:
- High prices compared to traditional values (e.g., by taking the present value of their cash flows for the duration of the asset and comparing it with their interest rates).
- Conditons incompatible with long-term growth (e.g., extrapolating past revenue and earnings growth rates late in the cycle).
- Many new and inexperienced buyers were drawn in by the perceived hot market.
- Broad bullish sentiment.
- Debt financing a large portion of purchases.
- Lots of forward and speculative purchases to profit from price rises (e.g., inventories that are more than needed, contracted forward purchases, etc.).
I use these criteria to assess all markets for bubbles. I have periodically shown you these for stocks and the stock market.
What Was Shown in January Versus Now
I will first describe the picture in words, then show it in charts, and compare it to the last update in January.
As of January, the bubble indicator showed that a) the US equity market was in a moderate bubble, but not an extreme one (ie., 70 percent of way toward the highest bubble, which occurred in the late 1990s and late 1920s), and b) the emerging tech companies (ie. As well, the unprecedented flood of liquidity post-COVID financed other bubbly behavior (e.g. SPACs, IPO boom, big pickup in options activity), making things bubbly. I showed which stocks were in bubbles and created an index of those stocks, which I call “bubble stocks.”
Those bubble stocks have popped. They fell by a third last year, while the S&P 500 remained flat. In light of these and other market developments, it is not necessarily true that now is a good time to buy emerging tech stocks.
The fact that they aren't at a bubble extreme doesn't mean they are safe or that it's a good time to get long. Our metrics still show that US stocks are overvalued. Once popped, bubbles tend to overcorrect to the downside rather than settle at “normal” prices.
The following charts paint the picture. The first shows the US equity market bubble gauge/indicator going back to 1900, currently at the 40% percentile. The charts also zoom in on the gauge in recent years, as well as the late 1920s and late 1990s bubbles (during both of these cases the gauge reached 100 percent ).
The chart below depicts the average bubble gauge for the most bubbly companies in 2020. Those readings are down significantly.
The charts below compare the performance of a basket of emerging tech bubble stocks to the S&P 500. Prices have fallen noticeably, giving up most of their post-COVID gains.
The following charts show the price action of the bubble slice today and in the 1920s and 1990s. These charts show the same market dynamics and two key indicators. These are just two examples of how a lot of debt financing stock ownership coupled with a tightening typically leads to a bubble popping.
Everything driving the bubbles in this market segment is classic—the same drivers that drove the 1920s bubble and the 1990s bubble. For instance, in the last couple months, it was how tightening can act to prick the bubble. Review this case study of the 1920s stock bubble (starting on page 49) from my book Principles for Navigating Big Debt Crises to grasp these dynamics.
The following charts show the components of the US stock market bubble gauge. Since this is a proprietary indicator, I will only show you some of the sub-aggregate readings and some indicators.
Each of these six influences is measured using a number of stats. This is how I approach the stock market. These gauges are combined into aggregate indices by security and then for the market as a whole. The table below shows the current readings of these US equity market indicators. It compares current conditions for US equities to historical conditions. These readings suggest that we’re out of a bubble.
1. How High Are Prices Relatively?
This price gauge for US equities is currently around the 50th percentile.
2. Is price reduction unsustainable?
This measure calculates the earnings growth rate required to outperform bonds. This is calculated by adding up the readings of individual securities. This indicator is currently near the 60th percentile for the overall market, higher than some of our other readings. Profit growth discounted in stocks remains high.
Even more so in the US software sector. Analysts' earnings growth expectations for this sector have slowed, but remain high historically. P/Es have reversed COVID gains but remain high historical.
3. How many new buyers (i.e., non-existing buyers) entered the market?
Expansion of new entrants is often indicative of a bubble. According to historical accounts, this was true in the 1990s equity bubble and the 1929 bubble (though our data for this and other gauges doesn't go back that far). A flood of new retail investors into popular stocks, which by other measures appeared to be in a bubble, pushed this gauge above the 90% mark in 2020. The pace of retail activity in the markets has recently slowed to pre-COVID levels.
4. How Broadly Bullish Is Sentiment?
The more people who have invested, the less resources they have to keep investing, and the more likely they are to sell. Market sentiment is now significantly negative.
5. Are Purchases Being Financed by High Leverage?
Leveraged purchases weaken the buying foundation and expose it to forced selling in a downturn. The leverage gauge, which considers option positions as a form of leverage, is now around the 50% mark.
6. To What Extent Have Buyers Made Exceptionally Extended Forward Purchases?
Looking at future purchases can help assess whether expectations have become overly optimistic. This indicator is particularly useful in commodity and real estate markets, where forward purchases are most obvious. In the equity markets, I look at indicators like capital expenditure, or how much businesses (and governments) invest in infrastructure, factories, etc. It reflects whether businesses are projecting future demand growth. Like other gauges, this one is at the 40th percentile.
What one does with it is a tactical choice. While the reversal has been significant, future earnings discounting remains high historically. In either case, bubbles tend to overcorrect (sell off more than the fundamentals suggest) rather than simply deflate. But I wanted to share these updated readings with you in light of recent market activity.
Bradley Vangelder
3 years ago
How we started and then quickly sold our startup
From a simple landing where we tested our MVP to a platform that distributes 20,000 codes per month, we learned a lot.
Starting point
Kwotet was my first startup. Everyone might post book quotes online.
I wanted a change.
Kwotet lacked attention, thus I felt stuck. After experiencing the trials of starting Kwotet, I thought of developing a waitlist service, but I required a strong co-founder.
I knew Dries from school, but we weren't close. He was an entrepreneurial programmer who worked a lot outside school. I needed this.
We brainstormed throughout school hours. We developed features to put us first. We worked until 3 am to launch this product.
Putting in the hours is KEY when building a startup
The instant that we lost our spark
In Belgium, college seniors do their internship in their last semester.
As we both made the decision to pick a quite challenging company, little time was left for Lancero.
Eventually, we lost interest. We lost the spark…
The only logical choice was to find someone with the same spark we started with to acquire Lancero.
And we did @ MicroAcquire.
Sell before your product dies. Make sure to profit from all the gains.
What did we do following the sale?
Not far from selling Lancero I lost my dad. I was about to start a new company. It was focused on positivity. I got none left at the time.
We still didn’t let go of the dream of becoming full-time entrepreneurs. As Dries launched the amazing company Plunk, and I’m still in the discovering stages of my next journey!
Dream!
You’re an entrepreneur if:
You're imaginative.
You enjoy disassembling and reassembling things.
You're adept at making new friends.
YOU HAVE DREAMS.
You don’t need to believe me if I tell you “everything is possible”… I wouldn't believe it myself if anyone told me this 2 years ago.
Until I started doing, living my dreams.
Antonio Neto
3 years ago
What's up with tech?
Massive Layoffs, record low VC investment, debate over crash... why is it happening and what’s the endgame?
This article generalizes a diverse industry. For objectivity, specific tech company challenges like growing competition within named segments won't be considered. Please comment on the posts.
According to Layoffs.fyi, nearly 120.000 people have been fired from startups since March 2020. More than 700 startups have fired 1% to 100% of their workforce. "The tech market is crashing"
Venture capital investment dropped 19% QoQ in the first four months of 2022, a 2018 low. Since January 2022, Nasdaq has dropped 27%. Some believe the tech market is collapsing.
It's bad, but nothing has crashed yet. We're about to get super technical, so buckle up!
I've written a follow-up article about what's next. For a more optimistic view of the crisis' aftermath, see: Tech Diaspora and Silicon Valley crisis
What happened?
Insanity reigned. Last decade, everyone became a unicorn. Seed investments can be made without a product or team. While the "real world" economy suffered from the pandemic for three years, tech companies enjoyed the "new normal."
COVID sped up technology adoption on several fronts, but this "new normal" wasn't so new after many restrictions were lifted. Worse, it lived with disrupted logistics chains, high oil prices, and WW3. The consumer market has felt the industry's boom for almost 3 years. Inflation, unemployment, mental distress...what looked like a fast economic recovery now looks like unfulfilled promises.
People rethink everything they eat. Paying a Netflix subscription instead of buying beef is moronic if you can watch it for free on your cousin’s account. No matter how great your real estate app's UI is, buying a house can wait until mortgage rates drop. PLGProduct Led Growth (PLG) isn't the go-to strategy when consumers have more basic expense priorities.
Exponential growth and investment
Until recently, tech companies believed that non-exponential revenue growth was fatal. Exponential growth entails doing more with less. From Salim Ismail words:
An Exponential Organization (ExO) has 10x the impact of its peers.
Many tech companies' theories are far from reality.
Investors have funded (sometimes non-exponential) growth. Scale-driven companies throw people at problems until they're solved. Need an entire closing team because you’ve just bought a TV prime time add? Sure. Want gold-weight engineers to colorize buttons? Why not?
Tech companies don't need cash flow to do it; they can just show revenue growth and get funding. Even though it's hard to get funding, this was the market's momentum until recently.
The graph at the beginning of this section shows how industry heavyweights burned money until 2020, despite being far from their market-share seed stage. Being big and being sturdy are different things, and a lot of the tech startups out there are paper tigers. Without investor money, they have no foundation.
A little bit about interest rates
Inflation-driven high interest rates are said to be causing tough times. Investors would rather leave money in the bank than spend it (I myself said it some days ago). It’s not wrong, but it’s also not that simple.
The USA central bank (FED) is a good proxy of global economics. Dollar treasury bonds are the safest investment in the world. Buying U.S. debt, the only country that can print dollars, guarantees payment.
The graph above shows that FED interest rates are low and 10+ year bond yields are near 2018 levels. Nobody was firing at 2018. What’s with that then?
Full explanation is too technical for this article, so I'll just summarize: Bond yields rise due to lack of demand or market expectations of longer-lasting inflation. Safe assets aren't a "easy money" tactic for investors. If that were true, we'd have seen the current scenario before.
Long-term investors are protecting their capital from inflation.
Not a crash, a landing
I bombarded you with info... Let's review:
Consumption is down, hurting revenue.
Tech companies of all ages have been hiring to grow revenue at the expense of profit.
Investors expect inflation to last longer, reducing future investment gains.
Inflation puts pressure on a wheel that was rolling full speed not long ago. Investment spurs hiring, growth, and more investment. Worried investors and consumers reduce the cycle, and hiring follows.
Long-term investors back startups. When the invested company goes public or is sold, it's ok to burn money. What happens when the payoff gets further away? What if all that money sinks? Investors want immediate returns.
Why isn't the market crashing? Technology is not losing capital. It’s expecting change. The market realizes it threw moderation out the window and is reversing course. Profitability is back on the menu.
People solve problems and make money, but they also cost money. Huge cost for the tech industry. Engineers, Product Managers, and Designers earn up to 100% more than similar roles. Businesses must be careful about who they keep and in what positions to avoid wasting money.
What the future holds
From here on, it's all speculation. I found many great articles while researching this piece. Some are cited, others aren't (like this and this). We're in an adjustment period that may or may not last long.
Big companies aren't laying off many workers. Netflix firing 100 people makes headlines, but it's only 1% of their workforce. The biggest seem to prefer not hiring over firing.
Smaller startups beyond the seeding stage may be hardest hit. Without structure or product maturity, many will die.
I expect layoffs to continue for some time, even at Meta or Amazon. I don't see any industry names falling like they did during the .com crisis, but the market will shrink.
If you are currently employed, think twice before moving out and where to.
If you've been fired, hurry, there are still many opportunities.
If you're considering a tech career, wait.
If you're starting a business, I respect you. Good luck.